Aldehyde dehydrogenase (EC 1.2.1.3), an enzyme responsible for metabolism of more than 90% of ethanol-derived acetaldehyde, consists of isozymes which are products of distinct genetic loci and exhibit subcellular organelle distribution specificity suggesting their functional importance in cellular differentiation and development. The "alcohol flush reaction" in Orientals has been correlated recently with a "missing isozyme of aldehyde dehydrogenase. The objective of this proposal is the characterization of the isozymes of human aldehyde dehydrogenase employing physicochemical methods as well as kinetic and spectroscopic procedures (combined with chemical modification by inhibitors) and to study subcellular and organ distribution of the isozymes. The results of the proposed investigation will provide information about the number of isozymes, their properties with respect to acetaldehyde, their structural interrelationships (identifying gene loci), presence ob allozymes, and their possible involvement in metabolic regulation. Further, the results will provide knowledge of the mechanism of action of inhibitors, which can be useful as therapeutic agents, and insight into the physiological roles of the isozymes. Such knowledge is essential for a basic understanding and rational interpretation of research carried out under the Institute's priorities, e.g., "Genetic Factors in Alcoholism", "Fetal Alcohol Syndrome" and "Alcoholism in Women". It should also allow us to understand specific features of the widely held global hypothesis that acetaldehyde arising from alcohol metabolism competes with aldehyde metabolites of biogenic amines and corticosteroids for the "same" enzyme. This hypothesis will assuredly need modification in light of specific properties of the isozymes which constitute "the" enzyme.